Estimating causal effects of treatment in RCTs with provider and subject noncompliance.

Subject noncompliance is a common problem in the analysis of randomized clinical trials (RCTs). With cognitive behavioral interventions, the addition of provider noncompliance further complicates making causal inference. As a motivating example, we consider an RCT of a motivational interviewing (MI)-based behavioral intervention for treating problem drug use. Treatment receipt depends on compliance of both a therapist (provider) and a patient (subject), where MI is received when the therapist adheres to the MI protocol and the patient actively participates in the intervention. However, therapists cannot be forced to follow protocol and patients cannot be forced to cooperate in an intervention. In this article, we (1) define a causal estimand of interest based on a principal stratification framework, the average causal effect of treatment among provider-subject pairs that comply with assignment or ACE(cc); (2) explore possible assumptions that identify ACE(cc); (3) develop novel estimators of ACE(cc); (4) evaluate estimators' statistical properties via simulation; and (5) apply our proposed methods for estimating ACE(cc) to data from our motivating example.

When the "U" is not Inverted: Trajectories of Expressed Emotional Arousal Predict Relationship Satisfaction.

Maladaptive emotional reactivity and dysfunctional communication during couple conflict are both destructive to couple functioning, and observational research has elucidated how conflict escalates. However, much of the evidence is based on measures that combine content (i.e., what was said) and the emotion with which it was said, which are then examined using sequential analyses. Despite the general presumptions about underlying emotional reactivity and escalation in negative emotions as part of relationship distress and deterioration, little empirical data are available that directly examine these continuous shifts in emotions. The current study examined concurrent and longitudinal associations between relationship satisfaction and trajectories of change in vocally expressed emotional arousal during couple conflict in 62 couples who participated in a relationship education program. Contrary to expectations and patterns found in distressed couples, trajectories followed a U-shape rather than an inverted U-shape curve, with steeper and more persistent decreases in emotional arousal predicting more stable relationship satisfaction over time. In addition, there were within-couple effects. These results suggest that early signs for relationship deterioration may be less in the form of overt escalation as would be seen in distressed couples. Instead, couples who subsequently deteriorate more are less effective in calming emotional arousal. They also are less able to remain at lower emotional arousal. It is possible that the more pronounced escalation toward the end of the conversation in more at-risk couples is a precursor of the greater escalation patterns seen in distressed couples; this should be examined empirically. Limitations and implications are discussed.

La reactividad emocional desadaptativa y la comunicación disfuncional durante el conflicto de pareja son destructivas para el funcionamiento de la pareja, y la investigación observacional ha dilucidado cómo escala el conflicto. Sin embargo, gran parte de la evidencia está basada en mediciones que combinan el contenido (p. ej.: lo que se dijo) y la emoción con la que se dijo, que luego se analizan usando análisis secuenciales. A pesar de las presunciones generales acerca de la reactividad emocional subyacente y la escalada de las emociones negativas como parte del distrés y el deterioro de la relación, existen pocos datos empíricos que analicen directamente estos cambios continuos en las emociones. El presente estudio analizó las asociaciones simultáneas y longitudinales entre la satisfacción con la relación y las trayectorias de cambio en la agitación emocional expresada vocalmente durante el conflicto de pareja en 62 parejas que participaron en un programa de capacitación en relaciones. Contrariamente a las expectativas y los patrones hallados en las parejas problemáticas, las trayectorias siguieron una forma de U en lugar de una curva con forma de U invertida, con disminuciones más pronunciadas y más constantes de la agitación emocional que predicen una satisfacción más estable con la relación en el transcurso del tiempo. Además, hubo efectos dentro de la pareja. Estos resultados sugieren que las primeras señales de deterioro de la relación pueden ser menores en forma de escalada abierta de lo que se vería en las parejas problemáticas. En cambio, las parejas que posteriormente se deterioran más son menos eficaces a la hora de calmar la agitación emocional. También son menos capaces de permanecer en una agitación emocional más baja. Es posible que la escalada más pronunciada hacia el final de la conversación en las parejas con mayor riesgo sea una precursora de los patrones de mayor escalada observados en las parejas problemáticas; esto debería analizarse empíricamente. Se debaten las limitaciones y las consecuencias.

Hypothesis testing for differentially correlated features.

In a multivariate setting, we consider the task of identifying features whose correlations with the other features differ across conditions. Such correlation shifts may occur independently of mean shifts, or differences in the means of the individual features across conditions. Previous approaches for detecting correlation shifts consider features simultaneously, by computing a correlation-based test statistic for each feature. However, since correlations involve two features, such approaches do not lend themselves to identifying which feature is the culprit. In this article, we instead consider a serial testing approach, by comparing columns of the sample correlation matrix across two conditions, and removing one feature at a time. Our method provides a novel perspective and favorable empirical results compared with competing approaches.

A new synthesis analysis method for building logistic regression prediction models.

Synthesis analysis refers to a statistical method that integrates multiple univariate regression models and the correlation between each pair of predictors into a single multivariate regression model. The practical application of such a method could be developing a multivariate disease prediction model where a dataset containing the disease outcome and every predictor of interest is not available. In this study, we propose a new version of synthesis analysis that is specific to binary outcomes. We show that our proposed method possesses desirable statistical properties. We also conduct a simulation study to assess the robustness of the proposed method and compare it to a competing method.

DUOX2 variants associate with preclinical disturbances in microbiota-immune homeostasis and increased inflammatory bowel disease risk.

A primordial gut-epithelial innate defense response is the release of hydrogen peroxide by dual NADPH oxidase (DUOX). In inflammatory bowel disease (IBD), a condition characterized by an imbalanced gut microbiota-immune homeostasis, DUOX2 isoenzyme is the highest induced gene. Performing multiomic analyses using 2872 human participants of a wellness program, we detected a substantial burden of rare protein-altering DUOX2 gene variants of unknown physiologic significance. We identified a significant association between these rare loss-of-function variants and increased plasma levels of interleukin-17C, which is induced also in mucosal biopsies of patients with IBD. DUOX2-deficient mice replicated increased IL-17C induction in the intestine, with outlier high Il17c expression linked to the mucosal expansion of specific Proteobacteria pathobionts. Integrated microbiota/host gene expression analyses in patients with IBD corroborated IL-17C as a marker for epithelial activation by gram-negative bacteria. Finally, the impact of DUOX2 variants on IL-17C induction provided a rationale for variant stratification in case control studies that substantiated DUOX2 as an IBD risk gene. Thus, our study identifies an association of deleterious DUOX2 variants with a preclinical hallmark of disturbed microbiota-immune homeostasis that appears to precede the manifestation of IBD.

Removing very low-performing therapists: A simulation of performance-based retention in psychotherapy.

Therapists can impact the likelihood a given patient will benefit from psychotherapy. However, therapists are rarely held accountable for their patients' outcomes. As a result, low-performing providers likely continue to practice alongside providers with high response rates. In the current study, we conducted a Monte Carlo simulation to illustrate a thought experiment-what happens to patient outcomes if therapists with the worst outcomes were removed from practice? We drew initial samples of 50 therapists from 3 simulated populations of 1,000 therapists with a mean patient response rate of 50% and different effect sizes for therapist variability in outcomes. We simulated 30 patient outcomes for each therapist, with outcome defined as response to treatment versus no response. We removed therapists with response rates in the bottom 5% and replaced them with a random sample of therapists from the population. Over 10 years, the difference in responses between the lowest and highest performing therapists was substantial (between 697 and 997 additional responses to treatment). After repeatedly removing the lowest performing providers 40 times (simulating a 10-year time span), response rates increased substantially. The cumulative number of patient responses (i.e., summing the total number of responses across 10 years) increased by 4,266, 6,404, and 9,307 when therapists accounted for 5%, 10%, or 20% of the patient outcome variance, respectively. These findings indicate that performance-based retention of therapists could improve the quality of psychotherapy in health systems by improving the average response rate and decreasing the probability that a patient will be treated by a therapist who consistently has poor outcomes.

Behaviorally-based couple therapies reduce emotional arousal during couple conflict.

Emotional arousal during relationship conflict is a major target for intervention in couple therapies. The current study examines changes in conflict-related emotional arousal in 104 couples that participated in a randomized clinical trial of two behaviorally-based couple therapies. Emotional arousal is measured using mean fundamental frequency of spouse's speech, and changes in emotional arousal from pre-to post-therapy are examined using multilevel models. Overall emotional arousal, the rate of increase in emotional arousal at the beginning of conflict, and the duration of emotional arousal declined for all couples. Reductions in overall arousal were stronger for TBCT wives than for IBCT wives but not significantly different for IBCT and TBCT husbands. Reductions in the rate of initial arousal were larger for TBCT couples than IBCT couples. Reductions in duration were larger for IBCT couples than TBCT couples. These findings suggest that both therapies can reduce emotional arousal, but that the two therapies create different kinds of change in emotional arousal.

More than reflections: empathy in motivational interviewing includes language style synchrony between therapist and client.

Empathy is a basic psychological process that involves the development of synchrony in dyads. It is also a foundational ingredient in specific, evidence-based behavioral treatments like motivational interviewing (MI). Ratings of therapist empathy typically rely on a gestalt, "felt sense" of therapist understanding and the presence of specific verbal behaviors like reflective listening. These ratings do not provide a direct test of psychological processes like behavioral synchrony that are theorized to be an important component of empathy in psychotherapy. To explore a new objective indicator of empathy, we hypothesized that synchrony in language style (i.e., matching how statements are phrased) between client and therapists would predict gestalt ratings of empathy over and above the contribution of reflections. We analyzed 122 MI transcripts with high and low empathy ratings based on the Motivational Interviewing Treatment Integrity global rating scale. Linguistic inquiry and word count was used to estimate language style synchrony (LSS) of adjacent client and therapist talk turns. High-empathy sessions showed greater LSS across 11 language style categories compared with low-empathy sessions (p<.01), and overall, average LSS was notably higher in high-empathy versus low-empathy sessions (d=0.62). Regression analyses showed that LSS was predictive of empathy ratings over and above reflection counts; a 1 SD increase in LSS is associated with a 2.4 times increase in the odds of a high-empathy rating, controlling for therapist reflections (odds ratio=2.4; 95% CI: 1.36; 4.24, p<.01). These findings suggest empathy ratings are related to synchrony in language style, over and above synchrony of content as measured by therapist reflections. Novel indicators of therapist empathy may have implications for the study of MI process as well as the training of therapists.

Friend or foe: Personal use and friends' use of protective behavioral strategies and spring break drinking.

The present study examined associations between use of protective behavioral strategies (PBS) by college students and their friends and drinking-related outcomes during Spring Break (SB). Moreover, this study examined the influence of friends' own PBS use on participants' PBS use during SB. Participants included college students (N = 694) and their nominated friends (N = 131) who were part of a larger study of SB drinking. Data were collected via web-based surveys that participants and friends took after SB, which assessed SB PBS, drinking, and related negative consequences. Results indicated that higher levels of Serious Harm Reduction (SHR) strategies and Limiting/Stopping (LS) strategies were associated with increased consumption, higher likelihood of experiencing any consequences, and an increased number of consequences. A different pattern emerged for Manner of Drinking (MD) strategy use; participants utilizing higher levels of MD strategies drank less and had fewer consequences. LS and MD strategies used by the participant's friends appeared to have less of an impact on the participant's drinking outcomes. However, greater friends' use of SHR strategies was associated with increased alcohol use by the participant, but not with consequences. Greater friends' use of SHR strategies was associated with greater SHR strategy use by the participant. Friends' LS and MD strategies were not associated with participant drinking, consequences, or PBS. These findings highlight the potential utility of interventions that focus on drinking behaviors on specific high-risk occasions for those at risk as well as for their friends.